advances-in-protein-chemistry

The finishing stage of folding depends on the precise and specific sequence of amino acids, while previously folding stages are
supposed to be mostly insensitive to information of sequence [3].
Thermodynamics of Protein Conformational Changes
The folded conformation seems to be at narrow free energy (ΔG) state but any change in the folded conformation depends upon
the significant increment in free energy. The change in heat capacity when protein unfolding occurs is the temperature at which the
stability is high in its value. As far as free energy is concerned, the highest stability occurs when S=0, on the other hand calculation by the
equilibrium constant appears when enthalpy change is zero. The maximum stabilities could be occurred at different temperature ranges,
but both are considered in different cases. The stabilities of native form decrease at both lower and higher temperatures.
The other factors such as binding interactions among the amino acids seem to be playing an elaborative role in the stability of the
protein conformation but these are not responsible for the significant stability and similar situation happens in the unfolded state, while
the bonding between native protein and solvent is expected to be strong enough as compared to the bonding between unfolded coil and
the surrounding environment. Moreover, the hydrophobic effect is considered to be the major stabilizing player.
Energy Landscape Theory and Thermodynamics of Protein Stability
Protein folding is one of the complex processes. Frauenfelder et al. and Bryngelson et al. describe the complexity of protein folding by
restoring to a statistical approach to the energetic of protein conformation in the form of energy landscape [4-5]. Bryngelson et al. refers
it mathematical procedure that assist in understanding of microscopic behavior of molecular system. It gives quantitative explanations
of folded protein state, ensembles of conformational sub-states, ensembles of folding intermediates and denatured or unfolded states and
considered as the realistic model of protein [6-7]. Bryngelson et al. describes an energy landscape, in mathematical form, of a system with
“n” degrees of freedom is an energy function [5]:
F(x) = F(x 1
, x 2
, x 3
,..., x n
)
Here, x 1
, x 2
, x 3
,…, x n
are variables for the microscopic state of the system [8] and F(x) is defined as the free energy. As far as protein
is concerned, these variables (x 1
, x 2
, x 3
,…, x n
) are all the dihedral angles of the chain and showing a single conformation of protein.
The stability of the protein can be determined by examining the set of values x 1
, x 2
, x 3
,…, x n
that gives minimum value of free energy
function, F(x). Moreover, the thermodynamics of protein stability is modeled reasonably well by the Energy Landscape Theory. Stability
of medium depends upon the ground and excited states of atoms and nuclear particles which are the simplest as well as basic models
while the understanding of complicated system like protein molecules contains far more complex idea and insight into ground and
excited states. The ground state of native structure is well illustrated by using energy landscape model where energy represents a function
of the topological alignment of atoms. Energy values generated by mountains and ridges are representation of spatial surface with the
large number of different co-ordinates.
Figure 2: Uses of Energy Landscape Models.
Protein Folding and Unfolding
Free and attached ribosomes are involved in the production of proteins within the biological system in the form of linear polypeptide
chain. The primary or linear structure is converted into stable three dimensional structures with the help of folding process. The whole
process of folding is controlled thermodynamically or kinetically by other proteins and/or enzymes, like molecular chaperones. The
process of folding represents that the information required for the precise folding is available in the polypeptide chain. On the other
hand, the three dimensional structure of proteins are damaged or affected by various reasons including miscoding due to errors in
protein synthesis and/or misfolding due to errors in protein folding.
Molecular Chaperones
The chaperones have significant impact on the process of protein folding. As far as their function is concerned, it belongs to the class
of proteins that assist in precise folding of proteins. The molecular chaperones are divided into following classes;
Class I chaperones exhibit the affinity to bind with the hydrophobic regions, subsequently preventing aggregation and unfolding
polymer is transported to various organelles.
Class II chaperones present inside the organelles assist in misfolding with the help of multiple bonds. It has been observed that when
cells are under stress proteins folding become improper.
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